Abstract Details

Title Davunetide for progressive supranuclear palsy: results of the AL-108-231, phase 2/3, 52 week, multi-center, randomized, double-blind, placebo-controlled clinical trial

Topic Movement Disorders

Presentation(s) (-)

Poster/Presentation
Number 007

Objective

Background Davunetide (AL-108) is an 8 amino acid peptide that promotes microtubule stability, decreases tau phosphorylation and improves memory in pre-clinical studies. Since PSP is tightly linked to tau pathology, we hypothesized that davunetide would be an effective treatment for PSP.

Design/Methods A double-blind, parallel group, clinical trial of davunetide 30 mg or matched placebo (randomized 1:1) administered intranasally twice daily for 52 weeks was conducted at 47 centers in North America, Europe and Australia. Participants were required to meet NINDS-SPSP criteria for possible or probable PSP, and were allowed to remain on stable doses of levodopa or coenzyme Q10. Co-primary outcomes were the PSP Rating Scale (PSPRS) and Schwab and England ADL (SEADL) scale. Safety was assessed by adverse events (AEs) and routine laboratory tests. Secondary outcomes included the Clinical Global Impression of Change (CGIC) and the change in brain atrophy on MRI.

Results 360 participants were screened, 313 were randomized and 243 (77.6%) completed the study. Baseline demographics and disease severity were similar between treatment groups. Mean age was 68±6.6, baseline PSPRS score was 40±11 and 94.2% (of 244 with available data) had the H1/H1 tau haplotype. There were no differences between davunetide and placebo-treated groups at 52 weeks in the PSPRS (p=0.41) or SEADL (p=0.92) scores. Mean PSPRS change was approximately 11±9 overall. There were also no group differences in CGIC scores (p=0.26) or MRI ventricular volumes (p= 0.77; n=215). There were 10 deaths in the davunetide group and 8 in the placebo group, with 54 serious AEs in each. Nasal AEs were more frequent in the davunetide group.

Conclusions Davunetide is not an effective treatment for PSP. PSP clinical trials are feasible and should be pursued with other promising tau-directed therapies.

Authors/Disclosures
Adam L. Boxer, MD, PhD (University of California, San Francisco)	An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project. Dr. Boxer has received research support from Rainwater Charitable Foundation.
Mark Gudesblatt, MD (South Shore Neurology Assoc. PC)	The institution of Dr. Gudesblatt has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for genentech. The institution of Dr. Gudesblatt has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen.
Anthony E. Lang, MD, FAAN (Toronto Western Hospital)	Dr. Lang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AbbVie, Amylyx, Aprinoia, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, BMS, Denali, Janssen, Lilly, Pharma 2B, Sun Pharma, and UCB. Dr. Lang has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for medicolegal cases related to paraquat. The institution of Dr. Lang has received research support from AbbVie. Dr. Lang has received intellectual property interests from a discovery or technology relating to health care. Dr. Lang has received publishing royalties from a publication relating to health care.
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
David S. Knopman, MD, FAAN (Mayo Clinic)	Dr. Knopman has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for DIAN TU study. The institution of Dr. Knopman has received research support from NIH.
Bruce L. Miller, MD, FAAN (University of California, San Francisco)	Dr. Miller has nothing to disclose.
Lon Schneider, MD (USC School of Medicine)	Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immue. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biovie. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Athira. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alpha-cognition. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Corium. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cortexyme. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurim Ltd. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Nordisk. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Otsuka. Dr. Schneider has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Schneider has received research support from NIH. The institution of Dr. Schneider has received research support from Eli Lilly. The institution of Dr. Schneider has received research support from Biogen. The institution of Dr. Schneider has received research support from Biohaven.
Rachelle S. Doody, MD, PhD	Dr. Doody has received personal compensation for serving as an employee of F. Hoffman-LaRoche. Dr. Doody has stock in F. Hoffman-LaRoche.
Andrew J. Lees, MD, FRCP (Reta Lila Weston Institute of Neurological Studies, IoN, UCL)	Dr. Lees has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Britannia. Dr. Lees has received personal compensation in the range of $5,000-$9,999 for serving as a Speaker with Bial Pharma.
	No disclosure on file
	No disclosure on file
Michael Gold, MD (Neumora Therapeutics)	No disclosure on file

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